These studies use participants in the Baltimore Longitudinal Study of Aging to gain insight into the genetic, biochemical and molecular mechanisms underlying age-associated changes in immune function. Grant=Z01AG00120 Longitudinal analysis of available data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program demonstrated a rise in the age-specific incidence of primary malignant brain tumors in the elderly between 1973 and 1985, in the United States. Strategies were developed to improve the treatment of malignant brain tumors. A novel lipophilic anticancer alkylating agent, a tertiarly butyl ester of chlorambucil, was developed. Anticholinesteroses were developed for treatment of Alzheimer's disease. The mechanism involved in reversible osmotic opening of the blood-brain barrier for brain therapy was elaborated. Low cerebrovascular permeability to vinca alkaloids, vincristine and vinblastine, was demonstrated and related to steric hindrance at the blood brain barrier. Brain pharmacokinetics of cyclophosphamide an alkylating anticancer drug, were quantified. Positively charged proteins were shown to be taken up from blood into brain via receptor mediated transcytosis, and may be used as drug carriers.